Our goal is to identify hair cell neurotransmitters. The strategy proposed can be successful even if the hair cell transmitter is not one of the known neurotransmitters, and even if many active substances are released from the hair cells. We have extracted and released active substances, presumably including the transmitter, from tissue that contains hair cells. The inner ears of Cyprinidae and Salmonidae fish, the tissues that we use as sources of active substances, are easily accessible and contain a large number of hair cells. Active substance(s) are detected by bioassays based on monitoring the activity of single fibers innervating the lateral line organs of Xenopus laevis or the bullfrog saccule. Active samples have been treated with cation-exchange resin in preliminary attempts to fractionate the samples, as a first step in the isolation of the active substance(s). This treatment removes the active substance(s) from common cations. The chemical properties of the active substance(s) will be determined by observing the effects of physical and chemical manipulation on the activity of the samples. The accumulated knowledge of chemical and physical properties will be used to separate and purify the active substances on a pilot scale. It will then be possible to design techniques for large scale purification, which will provide the amounts needed to identify the substances by mass spectroscopy or by peptide sequencing. Knowledge of the chemical properties may also permit identification of active substances as known compounds. Any substance present in tissue that contains hair cells and capable of affecting afferent nerve activity would be an excellent candidate to be a neurotransmitter in hair cell systems. Whether different kinds of hair cells release the same or similar transmitters can eventually be ascertained. Identifying the transmitter will allow the synthesis of the transmitter and the synthesis of drugs that block or mimic its actions. Such drugs could prove useful in reversibly alleviationg some of the symptoms of disorders of hearing and equilibration such as motion sickness, Meniere's syndrome, and peripheral tinnitus. If the transmitter has a trophic effect on auditory-nerve fibers, drugs that mimic that trophic action might prevent degeneration of the auditory nerve following hair cell loss, thereby allowing implantation of auditory prostheses to stimulate the auditory nerve.